Single-cell time series analysis reveals the dynamics of HSPC response to inflammation
Hematopoietic stem and progenitor cells (HSPCs) are known to respond to acute inflammation; however, little is understood about the dynamics and heterogeneity of these stress responses in HSPCs. Here, we performed single-cell sequencing during the sensing, response, and recovery phases of the inflam...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
March 2024
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| In: |
Life science alliance
Year: 2024, Volume: 7, Issue: 3, Pages: 1-17 |
| ISSN: | 2575-1077 |
| DOI: | 10.26508/lsa.202302309 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.26508/lsa.202302309 Verlag, lizenzpflichtig, Volltext: https://www.life-science-alliance.org/content/7/3/e202302309 
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| Author Notes: | Brigitte J. Bouman, Yasmin Demerdash, Shubhankar Sood, Florian Grünschläger, Franziska Pilz, Abdul R Itani, Andrea Kuck, Valérie Marot-Lassauzaie, Simon Haas, Laleh Haghverdi, Marieke AG Essers |
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| 245 | 1 | 0 | |a Single-cell time series analysis reveals the dynamics of HSPC response to inflammation |c Brigitte J. Bouman, Yasmin Demerdash, Shubhankar Sood, Florian Grünschläger, Franziska Pilz, Abdul R Itani, Andrea Kuck, Valérie Marot-Lassauzaie, Simon Haas, Laleh Haghverdi, Marieke AG Essers |
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| 520 | |a Hematopoietic stem and progenitor cells (HSPCs) are known to respond to acute inflammation; however, little is understood about the dynamics and heterogeneity of these stress responses in HSPCs. Here, we performed single-cell sequencing during the sensing, response, and recovery phases of the inflammatory response of HSPCs to treatment (a total of 10,046 cells from four time points spanning the first 72 h of response) with the proinflammatory cytokine IFN alpha to investigate the HSPCs' dynamic changes during acute inflammation. We developed the essential novel computational approaches to process and analyze the resulting single-cell time series dataset. This includes an unbiased cell type annotation and abundance analysis post inflammation, tools for identification of global and cell type-specific responding genes, and a semi-supervised linear regression approach for response pseudotime reconstruction. We discovered a variety of different gene responses of the HSPCs to the treatment. Interestingly, we were able to associate a global reduced myeloid differentiation program and a locally enhanced pyroptosis activity with reduced myeloid progenitor and differentiated cells after IFN alpha treatment. Altogether, the single-cell time series analyses have allowed us to unbiasedly study the heterogeneous and dynamic impact of IFN alpha on the HSPCs. | ||
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